Moricizine Side Effects

Cardiovascular

The multicenter Cardiac Arrhythmias Suppression Trial (CAST) failed to show improved survival during use of moricizine to treat asymptomatic or mildly asymptomatic premature ventricular depolarizations in patients with a recent history of myocardial infarction.

In a prospective study using maximal dosages of moricizine (mean 831 mg per day) in 31 patients with a history of sustained ventricular tachyarrhythmias (mean ejection fraction 0.39), a significant proarrhythmic effect and lack of efficacy were observed. Six of the 31 experienced ventricular proarrhythmias within four days. Of the remaining 25 patients, 24 underwent electrophysiologic testing and four were found to be noninducible (16% efficacy). Seven patients were discharged on moricizine therapy. One patient developed a ventricular proarrhythmia, one developed complete AV heart block, and two experienced recurrent ventricular tachycardia.[Ref]

Cardiovascular side effects have included exacerbation of old or induction of new atrial and ventricular arrhythmias (2% to 12%), heart failure (2%), hypotension (1%), and syncope (1%). Moricizine-induced arrhythmias may be lethal and more refractory to conversion to sinus rhythm than nondrug-induced arrhythmias. To reduce the proarrhythmic effect, it is recommended that the serum potassium, calcium, and magnesium concentrations be within normal limits prior to moricizine therapy.

Alteration in ventricular conduction, including new bundle branch patterns, has occurred in approximately 9.4% of patients. Second-degree heart block has occurred in patients without baseline conduction abnormalities (0.2%) as well as those with preexisting abnormalities (0.9%). Third-degree heartblock has been reported in 1.4% of patients with baseline conduction dysfunction.

Independent risk factors for the development of moricizine cardiotoxicity are advanced age, coronary artery disease, a history of myocardial infarction, low left ventricular ejection fraction (less than 0.40), and congestive heart failure.

Gastrointestinal

Gastrointestinal side effects occurred in up to 34% of patients, usually manifesting as nausea (10% to 34%), vomiting or diarrhea (2%), and abdominal discomfort (3%). Gastrointestinal effects were included in adverse reactions leading to discontinuation of therapy in 7% of patients. Anorexia, bitter taste, dysphagia, flatulence, and ileus have been reported.[Ref]

Nervous system

Nervous system side effects have usually manifest as dose-related dizziness (15%) and headache (8%). Other nervous system side effects included hypoesthesias (4%), paresthesias (2%), anxiety (3%), fatigue (1%), and sleep disorders (2%). Tremor, abnormal gait and coordination, ataxia, dyskinesia, confusion, somnolence, agitation, seizure, coma, speech disorder, and loss of memory have been reported.[Ref]

One case of increased parkinsonism has been reported. Moricizine is a phenothiazine derivative and suspected of exacerbating or inducing parkinsonian symptoms.[Ref]

Hematologic

No evidence of bone marrow toxicity was present in the rare reports of thrombocytopenia. Patients were on other drugs with thrombocytopenia-associated potential.[Ref]

Hematologic side effects have been rare, but have include thrombocytopenia.[Ref]